Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (666 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as cancer; apoptosis; and various neurological disorders. Clusterin is ubiquitously expressed and appears to function as a secreted molecular chaperone.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: SP 40,40 Protein; Apolipoprotein J; Complement Lysis Inhibitor; Complement-Associated Protein SP-40,40; Complement Associated Protein SP 40,40; SP-40,40, Complement-Associated Protein; Sulfated Glycoprotein 2; Sulfated Glycoprotein-2.
Where it fits in the MeSH classification
- Broader topics
- Glycoproteins; Molecular Chaperones
Related concepts
Research landscape
PubMed indexes 2,334 records tagged with the MeSH heading “Clusterin” (counts retrieved 2026-10-31). 398 of them (17.1%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 815 records.
Reviews account for 214 records (9.2%) and meta-analyses for 20. Randomized controlled trials number 13 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 521 |
| 2000-2009 | 600 |
| 2010-2019 | 815 |
| 2020 onward | 398 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 214 | 9.2% |
| Meta-analyses | 20 | 0.9% |
| Randomized controlled trials | 13 | 0.6% |
Method: PubMed query "Clusterin"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains.
- Closing excerpt
- These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (168 words)
Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both in vitro and in vivo, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu(-/-) mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 27148688 · DOI · PMC4917652
Clusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival [2]
Abstract reading summary — source excerpts
- Opening excerpt
- We define stress-induced adaptive survival pathways linking autophagy with the molecular chaperone clusterin (CLU) that function to promote anticancer treatment resistance.
- Closing excerpt
- This study defines a novel adaptor protein function for CLU under stress conditions, and highlights how co-targeting CLU and autophagy can amplify proteotoxic stress to delay cancer progression.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (124 words)
We define stress-induced adaptive survival pathways linking autophagy with the molecular chaperone clusterin (CLU) that function to promote anticancer treatment resistance. During treatment stress, CLU co-localizes with LC3 via an LIR-binding sequence within autophagosome membranes, functioning to facilitate LC3-Atg3 heterocomplex stability and LC3 lipidation, and thereby enhance autophagosome biogenesis and autophagy activation. Stress-induced autophagy is attenuated with CLU silencing in CLU(-/-) mice and human prostate cancer cells. CLU-enhanced cell survival occurs via autophagy-dependent pathways, and is reduced following autophagy inhibition. Combining CLU inhibition with anticancer treatments attenuates autophagy activation, increases apoptosis and reduces prostate cancer growth. This study defines a novel adaptor protein function for CLU under stress conditions, and highlights how co-targeting CLU and autophagy can amplify proteotoxic stress to delay cancer progression.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 25503391 · DOI · PMC4275590
Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundGenome-wide association studies have established clusterin (CLU) as a genetic modifier for late-onset Alzheimer's disease (AD).
- Closing excerpt
- ConclusionWe identify Clu as an astrocyte-derived synaptogenic and anti-amyloid factor; the combination of these activities may influence the progression of late-onset AD.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (217 words)
BackgroundGenome-wide association studies have established clusterin (CLU) as a genetic modifier for late-onset Alzheimer's disease (AD). Both protective and risk alleles have been identified which may be associated with its expression levels. However, the physiological function of clusterin in the central nervous system remains largely unknown.MethodsWe examined Clu expression in mouse brains by immunohistochemistry and high-resolution imaging. We performed electrophysiological recordings and morphological analysis of dendritic spines in wild-type and Clu knockout mice. We tested synaptic function of astrocytic Clu using neuron-glia co-cultures and by AAV-mediated astroglial Clu expression in vivo. Finally, we investigated the role of astrocytic Clu on synaptic properties and amyloid pathology in 5xFAD transgenic mouse model of AD.ResultsWe show that astrocyte secreted Clu co-localizes with presynaptic puncta of excitatory neurons. Loss of Clu led to impaired presynaptic function and reduced spine density in vivo. Neurons co-cultured with Clu-overexpressing astrocytes or treated with conditioned media from HEK293 cells transfected with Clu displayed enhanced excitatory neurotransmission. AAV-mediated astroglial Clu expression promoted excitatory neurotransmission in wild-type mice and rescued synaptic deficits in Clu knockout mice. Overexpression of Clu in the astrocytes of 5xFAD mice led to reduced Aβ pathology and fully rescued the synaptic deficits.ConclusionWe identify Clu as an astrocyte-derived synaptogenic and anti-amyloid factor; the combination of these activities may influence the progression of late-onset AD.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33517893 · DOI · PMC7849119
Clusterin Inhibits Neuronal Ferroptosis via the PI3K-AKT-mTOR-SREBP1 Axis to Promote Functional Recovery after Spinal Cord Injury [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Neuronal ferroptosis is considered as a key mechanism contributing to neurological deficits during the secondary injury phase following spinal cord injury (SCI).
- Closing excerpt
- In conclusion, this study reveals a novel mechanism whereby CLU promotes SCI repair by inhibiting neuronal ferroptosis via the PI3K-AKT-mTOR-SREBP1 axis, indicating its therapeutic potential for ferroptosis-targeted neuroprotective strategies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (157 words)
Neuronal ferroptosis is considered as a key mechanism contributing to neurological deficits during the secondary injury phase following spinal cord injury (SCI). Clusterin (CLU), a stress-responsive protein, has been reported to exert neuroprotective effects and promote neuronal survival in central nervous system injuries. However, its specific role in neuronal ferroptosis remains unclear. Here, we demonstrate that both exogenous recombinant CLU protein and endogenous CLU overexpression significantly inhibit neuronal ferroptosis, as evidenced by reduced lipid peroxidation, decreased iron accumulation, preserved mitochondrial integrity, and modulation of ferroptosis-related genes (upregulation of GPX4/xCT and downregulation of ACSL4). Mechanistically, CLU activates the PI3K-AKT-mTOR pathway, subsequently regulating the SREBP1-SCD1 lipid metabolism axis to suppress ACSL4-mediated lipid peroxidation. Furthermore, AAV-mediated CLU overexpression effectively mitigates pathological damage and significantly enhances motor function recovery in SCI mice. In conclusion, this study reveals a novel mechanism whereby CLU promotes SCI repair by inhibiting neuronal ferroptosis via the PI3K-AKT-mTOR-SREBP1 axis, indicating its therapeutic potential for ferroptosis-targeted neuroprotective strategies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41694601 · DOI · PMC12905574
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer [5]
- Research article Clusterin: a forgotten player in Alzheimer's disease [6]
- Research article Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases [7]
- Research article The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy [8]
- Research article Clusterin as a therapeutic target [9]
- Research article The molecular chaperone apolipoprotein J/clusterin as a sensor of oxidative stress: implications in therapeutic approaches - a mini-review [10]
References
- Cunin P, Beauvillain C, Miot C, Augusto JF, Preisser L, Blanchard S, et al.. Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses. . 2016. PMID 27148688 · DOI · PMC4917652
- Zhang F, Kumano M, Beraldi E, Fazli L, Du C, Moore S, et al.. Clusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival. . 2014. PMID 25503391 · DOI · PMC4275590
- Chen F, Swartzlander DB, Ghosh A, Fryer JD, Wang B, Zheng H. Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology. . 2021. PMID 33517893 · DOI · PMC7849119
- Yao S, Wang Z, Wang X, Yu Y, Huang X, Chen L, et al.. Clusterin Inhibits Neuronal Ferroptosis via the PI3K-AKT-mTOR-SREBP1 Axis to Promote Functional Recovery after Spinal Cord Injury. . 2026. PMID 41694601 · DOI · PMC12905574
- Shannan B, Seifert M, Leskov K, Willis J, Boothman D, Tilgen W, et al.. Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer. Cell Death Differ. 2006. PMID 16179938 · DOI
- Nuutinen T, Suuronen T, Kauppinen A, Salminen A. Clusterin: a forgotten player in Alzheimer's disease. Brain Res Rev. 2009. PMID 19651157 · DOI
- Trougakos IP, Gonos ES. Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases. Free Radic Res. 2006. PMID 17090421 · DOI
- Yu JT, Tan L. The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy. Mol Neurobiol. 2012. PMID 22274961 · DOI
- Wilson MR, Zoubeidi A. Clusterin as a therapeutic target. Expert Opin Ther Targets. 2017. PMID 27978767 · DOI
- Trougakos IP. The molecular chaperone apolipoprotein J/clusterin as a sensor of oxidative stress: implications in therapeutic approaches - a mini-review. Gerontology. 2013. PMID 23689375 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.